The goal of this project is to determine the control and organization of human spinal circuits that help coordinate movement and to understand possible malfunctioning of these circuits in movement disorders, particularly those with excessive muscle contraction: Stiffperson syndrome, dystonia, and spasticity. Progress was made in three areas during FY 1999. First, we examined supraspinal contributions to motor over-activity in patients with Stiffperson syndrome, using the technique of paired pulse transcranial magnetic stimulation, and found that the motor cortex exhibited excessive excitability. This may reflect loss of inhibitory cortical interneurons in this disorder. We also continue work on low frequency depression, which occurs when Ia stretch receptor afferents are repeatedly activated and is thought to result from properties intrinsic to the Ia terminal that regulate transmitter availability and release. We have hypothesized that early recruited motor units are more susceptible than late recruited units to depression, and furthermore, that this differential sensitivity will be lost in patients with spasticity, who have hyperactive stretch reflexes and clonus. Work in the past year focused on finding a reliable physiological marker to identify the size of a motor unit that would also allow assessment of the frequency response to Ia stimulation. Lastly, we continue to assess contributions of different classes of cutaneous afferents to simple reflexes in patients with peripheral neuropathies. Last year we found that patients with Fabrys disease, whose neuropathy predominantly affects small diameter sensory axons, have reduced cutaneous silent periods, a reflex that may serve a protective function, when the neuropathy is severe enough to produce insensitivity to non-noxious thermal stimulation. - movement disorders, spinal circuitry, spasticity, clinical neurophysiology, - Human Subjects